Introducing the brain: controls of sleep not here (Introduction)

by David Turell , Wednesday, August 16, 2023, 19:13 (463 days ago) @ David Turell

It is from the somatic body:

https://www.the-scientist.com/news/the-body-not-the-brain-regulates-sleep-71277

"Now, a new study published in Cell Reports has turned sleep research on its head. Researchers from the University of Tokyo and University of Tsukuba reported three key genes that are critical for regulating sleep—not in the brain, but in peripheral tissues. The findings demonstrate that sleep is all about protein homeostasis: endoplasmic reticulum (ER) stress and downregulation of protein biosynthesis in peripheral tissues trigger pathways that induce sleep.

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"Two of the mutations that Kawano and the team identified were in sel-1 and sel-11, which are involved in the degradation of misfolded proteins in the ER. Mutated worms showed protein accumulation via the unfolded protein response (UPR) pathway and subsequent ER stress.5

"The team also identified a third gene that affected worm sleep patterns, methionyl-tRNA synthetase (mars-1), which is critical for the translational initiation and elongation steps of protein biosynthesis. The team observed that in the mars-1 mutants, global translation was inhibited, leading to increased sleep in worms.

"Since sleep loss causes ER stress6 and impairs protein synthesis,7 Kawano and his colleagues believe that organisms cope with ER stress in peripheral tissues by signaling to the brain that sleep is required.

"The team next used tissue-specific promoters to rescue expression of these genes in different parts of the body and found that expression in the epidermis of the worms restored a normal sleep phenotype. With these results, the researchers confirmed, for the first time, that these three genes are involved in the regulation of sleep and they function specifically in peripheral tissues, with neuronal signaling occurring downstream of these pathways.

"Amita Sehgal, a neuroscientist at the University of Pennsylvania who was not involved in the study, was impressed with the team’s methods. “The authors of this study took an unbiased approach. They didn’t go in with any preconceived notions of what is required for sleep. With forward genetic screens, you let the animals tell you what’s important for sleep,” she commented.

"Lastly, the team performed experiments in mice to confirm that the same function is conserved in mammals. Both pharmacological and genetic inhibition of these same genes and pathways increased sleep duration in mice."

Comment: the results fit common sense. At the end of a day the body is filled with waste products that need to be dissipated. So, constant food and constant sleep are required for all living animal organisms.